Downregulating lncRNA PRNCR1 ameliorates LPS‐induced pulmonary vascular endothelial cell injury by modulating miR‐330‐5p/TLR4 axis

Abstract

Pulmonary vascular endothelial cell (PVEC) injury following acute lung injury or acute respiratory distress syndrome seriously affects disease development. Recently, accumulating evidence has suggested that long noncoding RNA (lncRNA) exerts significant effects in vascular endothelial cell injury. However, PRNCR1, a novel lncRNA, remains scarcely understood in terms of its functions in PVEC injury. Both in vivo and in vitro models of PVEC injury were constructed by lipopolysaccharide (LPS) administration. The relative expressions of PRNCR1, miR‐330‐5p, and TLR4 were detected by quantitative reverse transcription‐polymerase chain reaction, Western blot, and immunohistochemistry. Besides, gain and loss assays of PRNCR1/miR‐330‐5p were conducted to verify their effects on LPS‐induced PVEC injury. Cell Counting Kit‐8 assay used to measure cell viability and flow cytometry was used to detect apoptosis. Besides, the protein levels of caspase 3, nuclear factor‐κB (NF‐κB), and inflammatory cytokines (including tumor necrosis factor‐α, interleukin‐1β [IL‐1β], and IL‐6) were evaluated via Western blot and enzyme‐linked immunosorbent assay. Moreover, a dual‐luciferase activity experiment and RNA immunoprecipitation were applied to confirm the targeting relationship between PRNCR1 and miR‐330‐5p, miR‐330‐5p, and TLR4. PRNCR1 and TLR4 levels were significantly upregulated in LPS‐treated PVEC, both in vivo and in vitro, while miR‐330‐5p were downregulated. Inhibiting PRNCR1 or overexpressing miR‐330‐5p markedly attenuated LPS‐induced PVEC injury, expressions of TLR4, NF‐κB, and inflammatory cytokines. Mechanistically, PRNCR1 functioned as a competitive endogenous RNA by sponging miR‐330‐5p and then promoting TLR4 expression. PRNCR1 was upregulated in LPS‐induced PVEC and aggravated its injury via modulating the miR‐330‐5p/TLR4 axis.

Long non-coding PRNCR1 regulates the proliferation and apoptosis of synoviocytes in osteoarthritis by sponging miR-377-3p

“…Therefore, PRNCR1 overexpression may promote OA progression by promoting inflammatory responses. Our data and the previous study [ 12 ] suggested that PRNCR1 may play opposite roles in LPS-induced cell apoptosis in different cell types.…”

“…Previous studies of PRNCR1 have mainly focused on its role in cancers [ 25 , 26 ]. A recent study revealed the role of PRNCR1 in increasing pulmonary vascular endothelial cell injury induced by LPS via interacting with miR-330-5p/TLR4 axis [ 12 ]. It has been well-established that LPS-induced inflammation is a critical contributor to the development of OA.…”

“…Therefore, certain lncRNAs with critical roles in OA may be targeted to treat OA. PRNCR1 has been reported to promote LPS-induced inflammation [ 12 ], which contributes to osteoarthritis (OA) [ 13 ]. Besides that lncRNA PRNCR1 was reported to contribute to osteolysis via regulating CXCR4 expression [ 14 ] and osteogenic differentiation in osteolysis [ 15 ].…”

ATP2B1-AS1 Promotes Cerebral Ischemia/Reperfusion Injury Through Regulating the miR-330-5p/TLR4-MyD88-NF-κB Signaling Pathway

“…The biological functions of miR-330-5p are reported to be related with tumor progression, inflammation response, and oxidative stress ( Rambow et al, 2014 ; Feng et al, 2017 ; Xiao et al, 2018 ; Jin et al, 2020 ). Yu et al (2021) reported that the overexpression of miR-330-5p effectively reduced LPS-induced pulmonary vascular endothelial cell injury, and inhibited expressions of TLR4, NF-κB, and inflammatory cytokines. Xing et al (2020) investigated that miR-330-5p overexpression inhibited inflammation and oxidative stress by suppressing the TRAF6/NF-κB signaling in LPS-induced septic cardiomyopathy.…”

Genome-Wide Analysis of LncRNA in Bovine Mammary Epithelial Cell Injuries Induced by Escherichia Coli and Staphylococcus Aureus

“…Sponge function is one of the most important regulatory functions of lncRNAs. It has been found that lncRNAs can sequester microRNAs (miRNAs) to exercise the function of competing endogenous RNAs (ceRNAs) and participate in the regulation of cell proliferation, metastasis, inflammation, autophagy and apoptosis [ 25 ]. However, there are few studies on the involvement of lncRNAs in the regulation of bovine mastitis.…”